1. Field of the Invention
The extracorporeal treatment of blood to remove immunoglobulins and circulating immune complexes may be useful in a variety of circumstances. For example, it is suspected that some cancer patients develop a particular immune complex consisting of the patient's own IgG and an antigen associated with the cancer. It is thought that such complexes can interfere with the functioning of the patient's immune system and prevent the immune system from responding to the cancer. A system for adsorbing IgG can be used to remove the IgG complexes from the blood, allowing the patient's natural immune defenses to resume their proper function. In addition, a variety of "autoimmune" disorders involve the production of antibodies which are specific for the patient's own body. Severe harm can arise from such a misdirected immune response, causing illness and even death to the patient. Immunoadsorption of the antibodies may protect the body from further damage.
For these reasons, it is desirable to provide a system to facilitate removing antibodies from a patient's blood. It is particularly desirable that the device be convenient to use, sterile, and avoid the release of toxic substances into the blood being treated.
2. Description of the Prior Art
Heat and formalin-treated Staphylococcus aureus Cowan I packed in a column has been employed for the removal of IgG from blood. See, e.g., Jones et al. (1980) Cancer 46:675-684; Ray et al. (1980) Cancer 45:2633-2638; and Holohan et al. (1982) Cancer Res. 42:3663-3668. Such a system suffers from a number of disadvantages. Flow rate of plasma through the column is slow, and the column is subject to clogging. Moreover, possibly toxic bacterial cell wall components may be leached into the blood during the perfusion process. An improved system is described by Terman et al. (1981) N. Engl. J. Med. 305:1195-1200. Protein A is entrapped within a charcoal matrix and utilized to treat plasma. The system, however, is difficult to sterilize and it appears that there is significant loss of the protein A into the patient's blood (Balint et al. (1984) Cancer Res. 44:734-743). Blood treatment systems for the removal of anti-A and anti-B antibodies are described by Bensinger et al. (1981) N. Engl. J. Med. 304:160-162 and Bensinger et al. (1982) J. Clin. Apheresis 1:2-5. The immunoadsorption system utilizes synthetic human blood group antigens covalently linked to a silica matrix. The use of a protein A-silica column for extracorporeal immunoadsorption is briefly reported by Bensinger et al. (1982) N. Engl. J. Med. 306:935. "Affinity Chromatorgraphy--Principles and Methods" published by Pharmacia Fine Chemicals, Uppsala, Sweden, teaches that carbodiimide coupling to Sepharose.RTM. is best performed at a pH above 4.5.